| Title | Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors |
| Authors | Bakker, Mark K. van der Spek, Rick A. A. van Rheenen, Wouter Morel, Sandrine Bourcier, Romain Hostettler, Isabel C. Alg, Varinder S. van Eijk, Kristel R. Koido, Masaru Akiyama, Masato Terao, Chikashi Matsuda, Koichi Walters, Robin G. Lin, Kuang Li, Liming Millwood, Iona Y. Chen, Zhengming Rouleau, Guy A. Zhou, Sirui Rannikmae, Kristiina Sudlow, Cathie L. M. Houlden, Henry van den Berg, Leonard H. Dina, Christian Naggara, Olivier Gentric, Jean-Christophe Shotar, Eimad Eugene, Francois Desal, Hubert Winsvold, Bendik S. Borte, Sigrid Johnsen, Marianne Bakke Brumpton, Ben M. Sandvei, Marie Softeland Willer, Cristen J. Hveem, Kristian Zwart, John-Anker Verschuren, W. M. Monique Friedrich, Christoph M. Hirsch, Sven Schilling, Sabine Dauvillier, Jerome Martin, Olivier Winsvold, Bendik S. Winsvold, Bendik S. Borte, Sigrid Johnsen, Marianne Bakke Brumpton, Ben M. Sandvei, Marie Softeland Willer, Cristen J. Hveem, Kristian Zwart, John-Anker Bian, Zheng Chen, Junshi Chen, Yiping Chen, Zhengming Clarke, Robert Collins, Rory Guo, Yu Han, Xiao Hill, Michael Li, Liming Lin, Kuang Liu, Depei Lv, Jun Millwood, Iona Peto, Richard Sansome, Sam Walters, Robin Yang, Xiaoming Yu, Canqing Koido, Masaru Koido, Masaru Akiyama, Masato Terao, Chikashi Matsuda, Koichi Kamatani, Yoichiro Desal, Hubert Desal, Hubert Bourcier, Romain Redon, Richard Dina, Christian Naggara, Olivier Eugene, Francois Gentric, Jean-Christophe Shotar, Eimad Sargurupremraj, Muralidharan Tatlisumak, Turgut Debette, Stephanie Werring, David J. Houlden, Henry Alg, Varinder S. Hostettler, Isabel C. Bonner, Stephen Walsh, Daniel Bulters, Diederik Kitchen, Neil Brown, Martin Grieve, Joan Bakker, Mark K. Bourcier, Romain Walters, Robin G. Malik, Rainer Dichgans, Martin Sargurupremraj, Muralidharan Tatlisumak, Turgut Debette, Stephanie Rinkel, Gabriel J. E. Worrall, Bradford B. Pera, Joanna Slowik, Agnieszka Broderick, Joseph P. Werring, David J. Woo, Daniel Bijlenga, Philippe Kamatani, Yoichiro Ruigrok, Ynte M. Jones, Gregory T. Bown, Matthew J. Ko, Nerissa U. Kim, Helen Coleman, Jonathan R. I. Breen, Gerome Zaroff, Jonathan G. Klijn, Catharina J. M. Malik, Rainer Dichgans, Martin Sargurupremraj, Muralidharan Tatlisumak, Turgut Amouyel, Philippe Debette, Stephanie Rinkel, Gabriel J. E. Worrall, Bradford B. Pera, Joanna Slowik, Agnieszka Gaal-Paavola, Emilia I. Niemela, Mika Jaaskelainen, Juha E. von Und Zu Fraunberg, Mikael Lindgren, Antti Broderick, Joseph P. Werring, David J. Woo, Daniel Redon, Richard Bijlenga, Philippe Kamatani, Yoichiro Veldink, Jan H. Ruigrok, Ynte M. |
| Affiliation | Univ Utrecht, Dept Neurol & Neurosurg, Univ Med Ctr, Utrecht Brain Ctr, Utrecht, Netherlands Univ Geneva, Fac Med, Dept Pathol & Immunol, Geneva, Switzerland Geneva Univ Hosp, Fac Med, Dept Clin Neurosci, Neurosurg Div, Geneva, Switzerland Univ Nantes, Inst Thorax, CHU Nantes, CNRS,INSERM, Nantes, France CHU Nantes, Dept Neuroradiol, Nantes, France UCL, Stroke Res Ctr, Inst Neurol, London Queen Sq, London, England Tech Univ Munich, Dept Neurosurg, Klinikum Rechts Isar, Munich, Germany RIKEN Ctr Integrat Med Sci, Lab Stat & Translat Genet, Yokohama, Japan Univ Tokyo, Inst Med Sci, Dept Canc Biol, Tokyo, Japan Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Fukuoka, Japan Kyushu Univ, Grad Sch Med Sci, Dept Ocular Pathol & Imaging Sci, Fukuoka, Japan Univ Tokyo, Grad Sch Frontier Sci, Tokyo, Japan Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England Univ Oxford, Med Res Council, Populat Hlth Res Unit, Oxford, England Peking Univ, Sch Publ Hlth, Dept Epidmiol, Hlth Sci Ctr, Beijing, Peoples R China McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada Univ Edinburgh, Usher Inst, Ctr Med Informat, Edinburgh, Midlothian, Scotland UK Biobank, Stockport, Lancs, England Natl Hosp Neurol & Neurosurg, Neurogenet Lab, London, England Univ Paris 05, Necker Hosp Sick Children, Pediat Radiol, Paris, France St Anne Hosp, Dept Neuroradiol, F-S894 Paris, France Univ Paris 05, INSERM UMR, F-S894 Paris, France Univ Hosp Brest, Dept Neuroradiol, Brest, France Pite Salpetriere Hosp, Dept Neuroradiol, Brest, France Univ Hosp Rennes, Dept Neuroradiol, Rennes, France Oslo Univ Hosp, Dept Res Innovat & Educ, Div Clin Neurosci Innovat & Educ, Oslo, Norway Norwegian Univ Sci & Technol, KG Jebsen Ctr Genet Epidemiol, Dept Publ Hlth & Nursing, Fac Med & Hlth Sci, Trondheim, Norway Univ Oslo, Res & Commun Unit Musculoskeletal Hlth FORMI, Dept Res Innovat & Educ, Div Clin Neurosci, Oslo, Norway Univ Oslo, Inst Clin Med, Fac Med, Oslo, Oslo, Norway Norwegian Univ Sci & Technol, Fac Med & Hlth Sci, Dept Publ Hlth & Nursing, Trondheim, Norway Trondheim Reg & Univ Hosp, St Olavs Hosp, Canc Clin, Trondheim, Norway Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI USA Norwegian Univ Sci & Technol, Fac Med & Hlth Sci, Dept Publ Hlth & Nursing, HUNT Res Ctr, Trondheim, Norway Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands Natl Inst Publ Hlth & Environm, Bilthoven, Netherlands Dortmund Univ Appl Sci & Arts, Dortmund, Germany Univ Hosp Essen, Inst Med Informat Biometry & Epidmiol IMIBE, Essen, Germany Zurich Univ Appl Sci, Sch Life Sci & Facil Management, Zurich, Switzerland SIB Swiss Inst Bioinformat, Lausanne, Switzerland Univ Otago, Dept Surg, Dunedin, New Zealand Univ Leicester, Natl Inst Hlth Res, Dept Cardiovasc Sci, Leicester, England Univ Leicester, Glenfield Hosp, Leicester BioMed Res Ctr, Leicester, England Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA Univ Calif San Francisco, Ctr Cerebrovasc Res, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA Kings Coll London, Inst Psychiat Psychol & Neurosci, Social Genet & Dev Psychiat Ctr, London, England South London & Maudsley NHS Fdn Trust, UK Natl Inst Hlth Res NIHR, BRC, London, England Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Dept Neurol, Med Ctr, Nijmegen, Netherlands Ludwig Maximilians Univ Munchen, Inst Stroke & Dementia Res, Univ Hosp, Munich, Germany Munich Cluster Syst Neurol SyNergy, Munich, Germany Deutsch Zentrum Neurodegenerat Erkrankungen DZNE, Munich, Germany Univ Bordeaux, INSERM U1219 Bordeaux Populat Hlth Res Ctr, Bordeaux, France Bordeaux Univ Hosp, Inst Neurodegenerat Dis, Dept Neurol, Bordeaux, France Univ Gothenburg, Dept Clin Neurosci, Gothenburg, Sweden Univ Gothenburg, Inst Neurosci & Physiol, Gothenburg, Sweden AGE Univ Lille, Ctr Hosp Univ Lille Lille, Inst Pasteur Lille, INSERM,UMR1167 LabEx DISTALZ,RID, Lille, France Univ Virginia, Dept Neurol, Sch Med, Charlottesville, VA USA Univ Virginia, Dept Publ Hlth Sci, Sch Med, Charlottesville, VA USA Jagiellonian Univ, Fac Med, Dept Neurol, Med Coll, Krakow, Poland Univ Helsinki, Helsinki Univ Hosp, Dept Neurosurg, Helsinki, Finland Univ Helsinki, Clin Neurosci, Helsinki, Finland Kuopio Univ Hosp, Neurosurg NeuroCtr, Kuopio, Finland Univ Eastern Finland, Inst Clin Med, Fac Hlth Sci, Kuopio, Finland Univ Cincinnati, Coll Med, Cincinnati, OH USA Chinese Acad Med Sci, Beijing, Peoples R China China Natl Ctr Food Safety Risk Assessment, Beijing, Peoples R China James Cook Univ Hosp, Dept Anaesthesia, Middlesbrough, Cleveland, England Kings Coll Hosp NHS Fdn Trust, Dept Neurosurg, London, England Univ Hosp Southampton NHS Fdn Trust, Dept Neurosurg, Southampton, Hants, England Natl Hosp Neurol & Neurosurg, Dept Neurosurg, London, England |
| Keywords | LD SCORE REGRESSION SUBARACHNOID HEMORRHAGE GWAS METAANALYSIS SEX HERITABILITY VARIANTS SMOKING PATIENT GROWTH |
| Issue Date | Nov-2020 |
| Publisher | NATURE GENETICS |
| Abstract | Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of which are new. We reveal a polygenic architecture and explain over half of the disease heritability. We show a high genetic correlation between ruptured and unruptured intracranial aneurysms. We also find a suggestive role for endothelial cells by using gene mapping and heritability enrichment. Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepileptic and sex hormone drugs, providing insights into intracranial aneurysm pathophysiology. Finally, genetic risks for smoking and high blood pressure, the two main clinical risk factors, play important roles in intracranial aneurysm risk, and drive most of the genetic correlation between intracranial aneurysms and other cerebrovascular traits. Cross-ancestry genome-wide association analyses in individuals of European and East Asian ancestry identify 11 new risk loci for intracranial aneurysms and highlight a polygenic architecture explaining a substantial fraction of disease heritability. |
| URI | http://hdl.handle.net/20.500.11897/608068 |
| ISSN | 1061-4036 |
| DOI | 10.1038/s41588-020-00725-7 |
| Indexed | SCI(E) |
| Appears in Collections: | 公共卫生学院 |
